HLA-DPB1*0101 associations in UK Caucasian adult and juvenile idiopathic inflammatory myopathy patients.

Background: In the IIMs, HLA-DRB1*03 is strongly associated with the possession of anti-Jo-1 or -PM-Scl antibodies. Given the other clinical differences between these subgroups, we hypothesise that genetic differences also exist.Objectives: To investigate the HLA-DPB1 locus in adult and juvenile UK Caucasians with IIMs, and examine the relationship of DPB1 with HLA-DRB1 and myositis specific/associated antibodies (MSA/MAAs).Methods: 233 adult IIM patients (73% female, 49.4±13.6 years) with polymyositis (PM, n=89), dermatomyositis (DM, n=88) and myositis associated with another connective tissue disease (myositis/CTD-overlap, n=56) and 85 juvenile DM patients (JDM, 75% female, 6.2±3.6 years) defined with probable or definite disease according to Bohan and Peter, were compared to 678 randomly selected UK Caucasian controls. Patients and controls were genotyped at HLA-DPB1 and DRB1 using a commercially available sequence specific oligonucleotide kit. The types of detectable circulating MSA (anti-Jo-1, PL-7, PL-12, EJ, OJ, KS, Mi-2, SRP, 155/140) and MAA (U1/U3-RNP, Ku, PM-Scl) was also established.Results: HLA-DPB1*0101 was a significant risk factor in the combined IIM cases (22% vs. 13% controls, corrected probability (pcorr)=0.005, odds ratio [OR] 2.0, 95% confidence interval 1.4-2.8), also in PM (27%, pcorr=0.007, OR 2.5, 95% confidence interval 1.4-4.4) and in anti-Jo-1 antibody positive patients (n=51, 43%, pcorr=3.2 x 10-5, OR 4.1, 2.1-7.8), irrespective of clinical subtype. Linkage disequilibrium was noted between DPB1*0101 and DRB1*03 in controls (D prime=0.67). No other significant DPB1 associations were noted. Whilst HLA-DRB1*03 is known to be a strong risk factor for both anti-Jo-1 and -PM-Scl antibodies (Chinoy et al, 2006), there was no significant difference in the frequency of DPB*0101 between anti-PM-Scl (n=33, 15%) and controls (13%). After multiple corrections, no HLA-DPB1 associations were noted for DM, myositis/CTD-overlap or JDM vs. controls. In a multivariate logistic regression model, the PM and anti-Jo-1 DPB*0101 associations were both lost after adjusting for DRB1*03, which remained highly significant. No interaction was noted between these two alleles and no effect on gender was noted.Conclusion: HLA-DPB1*0101 is significantly associated with PM and anti-Jo-1 positive patients, although the association appears due to LD with DRB1*03. However, there is no significant association between anti-PM-Scl positive IIM patients and DPB*0101. This is the first data from the HLA region which appears to discriminate anti-Jo-1 from anti-PM-Scl IIM patients.References: Chinoy et al. (2006). Arthritis Res Ther, 8(1), R13.